Digital Commons Network^™

Reducing Storage-Related Bias In Reproductive Vitamin D Research: Towards A Stable And Reliable Biomarker Of Ovarian Vitamin D Status, Evelin E Lara-Molina, Jason M. Franasiak, Almudena Devesa-Peiro, Marina López-Nogueroles, Alberto Vázquez, David Amorós, Agustín Ballesteros, Antonio Pellicer, Patricia Sebastian-Leon, Patricia Diaz-Gimeno

SKMC Student Presentations and Publications

Background/Objectives: One of the main reasons for discrepancies in the role of vitamin D in ART could be the measurement of the conventional biomarker 25(OH)D₃. It is known that this value is affected by multiple factors, such as tissue origin, assay variability, classification criteria, and potential storage-related degradation. In this study, we investigate 24,25(OH)₂D₃ as a new biomarker to improve vitamin D assessment in women’s reproductive health, particularly regarding oocyte development. Methods: A prospective cohort study including 35 oocyte donors undergoing controlled ovarian stimulation, who were recruited between October and November 2017, was conducted. Vitamin …

A Double-Edged Sword: Ethical And Psychological Implications Of Apoe Genotype Disclosure Across The Lifespan, Diego Iacono

Department of Neurology Faculty Papers

The apolipoprotein E (APOE) gene is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), with the ε4 allele increasing risk and decreasing the average age of onset. While APOE genotyping is primarily used in research or clinical settings for patients with memory concerns, interest in disclosing APOE status to asymptomatic individuals—particularly during early adulthood—is growing. This trend is fueled by the rise of direct-to-consumer genetic testing and emerging prevention-focused clinical trials. However, ethical debates remain unresolved about the potential harms of early disclosure, including anxiety, stigma, and misunderstanding of probabilistic risk. Conversely, some argue that knowledge of APOE …

Multi-Omic Profiling Provides Insights Into The Heterogeneity, Microenvironmental Features, And Biomarker Landscape Of Small-Cell Lung Cancer, Mingchao Xie, Miljenka Vuko, Shashank Saran, Siyu Liu, Andrew G Chambers, Hana Baakza, Helen K Angell, Felicia Ng, Carl M Gay, Robert J Cardnell, Felix J Segerer, Alma Andoni, Jaime Rodriguez-Canales, Paul M Waring, Markus Schick, J Carl Barrett, Lauren A Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Background: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.

Methods: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.

Results: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest …

Inhibition Of Clostridioides Difficile-Specific Dna Adenine Methyltransferase Cama By Analogs Of S‑Adenosyl‑L‑Methionine, Jujun Zhou, Youchao Deng, Dan Yu, Taraneh Hajian, Masoud Vedadi, Xing Zhang, Robert M Blumenthal, Rong Huang, Xiaodong Cheng

Faculty, Staff and Student Publications

Epigenetically targeted therapies, especially those inhibiting S-adenosyl-l-methionine (SAM)-dependent methylations of DNA, mRNA, and histones, have advanced rapidly in cancer treatment. However, these therapies remain underexplored for antibiotic development, despite the growing threat of antimicrobial resistance. Here, we screened a focused library of SAM analogs against the DNA adenine methyltransferase CamA specific to the enteric pathogen Clostridioides difficile. At the same time, we examined six other adenine methyltransferases, including two bacterial DNA methyltransferases and four human RNA methyltransferases having distinct RNA substrates. Compound 113 selectively inhibited CamA (IC50 = 0.15 μM). In addition, compound 67 inhibited Caulobacter crescentus CcrM …

Hif-2-Dependent Regulation Of Pthrp And Paraneoplastic Hypercalcemia In Aggressive Clear-Cell Renal Cell Carcinoma, Arijit Mal, Bingqing Xie, Zane Gray, Charlotte Small, Susmita G Ramanand, Yunpeng Gao, Vanina Toffessi Tcheuyap, Sashi Debnath, Alana Christie, Jeffrey Miyata, Brooklyn Jackson, Hua Zhong, Boning Gao, Jay Lohrey, Naim M Maalouf, Sangeetha M Reddy, John D Minna, Ivan Pedrosa, Xiankai Sun, Ram S Mani, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) patients with hypercalcemia (HC) have worse outcomes. HC often involves PTHrP, and the role of HIF-2 is incompletely understood. Leveraging RCC tumorgraft (TG) models of HC, which were characterized by tumor cell autonomous inflamatory/immune signatures, we show that HIF-2 inhibition with PT2399 frequently normalized calcium, downregulated circulating PTHrP and reduced HIF-2 binding to the PTHLH (PTHrP) promoter. Likely contributing to the selective induction of PTHrP in a subset of HIF-2-dependent tumors, the PTHLH locus was generally more accessible in TG(HC). However, PTHLH chromatin accessibility was grossly unaffected by PT2399, unlike elsewhere (including EPO locus in a …

The Effectiveness Of A Chronic Care Management Program On Hospitalization Rates And Quality Of Life In Chronic Kidney Disease Patients, Sophie Burris

Doctoral Projects

Chronic Kidney Disease (CKD) is a progressive condition that distinctively affects underserved rural communities due to limited access to healthcare, provider shortages, and transportation barriers. Chronic Care Management (CCM) has emerged as a patient-centered, initiative-taking approach that emphasizes care coordination and self-management support. The purpose of this doctoral project was to evaluate the impact of implementing a CCM program in Caucasian females over the age of 40 with CKD residing in an underserved rural community post hospitalization. The Chronic Care Model (CCM) is the framework that guides the doctoral project which compared outcomes in patients enrolled in a CCM program …

Molecular Pathway Dysregulation In Chronic Liver Disease: Metabolic And Mechanotransductive Drivers Of Hepatic Pathophysiology, Samantha Harvat

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Metabolic dysfunction–associated steatotic liver disease (MASLD) represents a rapidly growing cause of chronic liver injury, yet the molecular interactions linking metabolic stress, inflammation, fibrosis, and hepatocellular carcinoma (HCC) remain incompletely defined. This thesis integrates transcriptomic analyses across multiple GEO datasets to identify coordinated metabolic, inflammatory, and mechanotransductive pathways that collectively drive disease progression.

Analysis of human liver biopsy datasets (GSE126848 and GSE89632) revealed consistent suppression of glycolysis, β-oxidation, and oxidative phosphorylation across MASLD and MASH samples, accompanied by modest compensatory TCA cycle activation. These alterations reflect impaired metabolic flexibility, mitochondrial stress, and increased ROS susceptibility. Concurrently, cytokine-network enrichment demonstrated activation …

From Standard To Stratified: Modeling Ntcp And Ear To Personalize Daily Mv-Cbct In Radiotherapy., Duong Thanh Tai, Luong Tien Phat, Tran Trung Kien, Duong Tuan Linh, Nguyen Ngoc Anh, Nguyen Quang Hung, Peter Sandwall, Parham Alaei, David Bradley, James C L Chow

Oncology Articles

PURPOSE: To evaluate the cumulative radiobiological impact of daily megavoltage cone-beam computed tomography (MV-CBCT) imaging dose based on normal tissue complication probability (NTCP) and excess absolute risk (EAR) of secondary malignancies among radiotherapy patients treated for breast, pelvic, and head & neck cancers. This study investigated whether MV-CBCT imaging dose warrants protocol personalization according to patient age, anatomical treatment site, and organ-specific radiosensitivity.

METHODS: This retrospective study included cohorts of breast (n = 30), pelvic (n = 17), and head & neck (n = 20) cancer patients undergoing radiotherapy with daily MV-CBCT. Imaging dose distributions employing two common MV-CBCT protocols …

A Novel Maturation Equation For Hepatic Clearance Across Preterm, Term Neonates, Children, And Adults: Application To Paracetamol And Its Metabolite, Yunjiao Wu, Swantje Völler, Sebastiaan C. Goulooze, Karel Allegaert, Catherine M.T. Sherwin, Anne Van Rongen, Daniëlla W. E. Roofthooft, Sinno H.P. Simons, Dick Tibboel, Robert B. Flint, John N. Van Den Anker, Catherijne A.J. Knibbe

Pediatrics Faculty Publications

A preterm and term neonate to adult (PTNA) maturation equation was introduced recently to describe the glomerular filtration rate maturation from birth to adulthood for neonates of varying gestational age. This study aims to evaluate the newly developed PTNA equation against common maturation approaches like allometric scaling (AS0.75), the AS0.75 plus postmenstrual age (PMA)-based Emax (AS0.75 + PMA) equation, and the bodyweight dependent exponent equation (BDE) for the maturation of three hepatic pathways of paracetamol (PCM) from preterm and term neonates up to adults. A population pharmacokinetic analysis was conducted with pooled plasma and urine data of PCM, PCM-glucuronide (PCM-GLU), …

Disruption Of The Placenta–Brain Axis In Transgenic Mice Lacking Serotonin Transporter (Sert) In Trophoblast Cells, David T. Ellenberger, Zhen Lyu, Rosalind T. B. Herrington, Jessica A. Kinkade, Gustavo W. Leone, Ji Ying Sze, Nathan J. Bivens, R. Frank Baker, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental–brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked …

Burden Of Neurodevelopmental Disorders In Kenyan Children, Symon Kariuki, Patricia Kipkemoi, Martha Kombe, Mary Bitta, Jacqueline Phillips Owen, Amina Abubakar, Charles Newton

Institute for Human Development, East Africa

Importance: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability contribute to one-tenth of the global burden of mental and neurologic disorders. The burden of NDDs is not well documented in Africa.

Objective:To assess the prevalence, risk factors, and comorbidities of NDDs in young Kenyan children.

Design, setting and participants: This cross-sectional study was conducted among children aged 6 to 9 years residing in the Kilifi Health and Demographic Surveillance System in Kenya. In stage I of the study, children were screened for NDDs from March 16, 2015, to September 14, 2016; those …

Breastfeeding Safety Following Maternal Anesthesia: A Guideline Development, Megan Honea, Mary Johnson

Doctoral Projects

Recommendations regarding breastfeeding following maternal anesthesia are inconsistent and often not up to date with current best practice guidelines. Previous recommendations have led to mothers unnecessarily “pumping and dumping” breast milk has benefits for both mother and baby. These benefits include (a) increasing the infant’s access to colostrum, (b) encouraging mother-baby bonding, (c) improving the mother’s breastfeeding experience, (d) and providing significant health benefits to the infant. The purpose of this scholarly project was to develop a set of evidence-based recommendations that focus on mothers who desire to breastfeed following general anesthesia. These recommendations will highlight maternal- fetal transfer of …

Integrating Spot-Scanning Proton Arc Therapy With Functional Avoidance Strategies To Reduce Pulmonary Toxicity, Yingxuan Chen, Peilin Liu, Xiaoda Cong, Edward Castillo, Richard Castillo, Inga Grills, Craig Stevens, Xiangkun Xu, Xiaoqiang Li, Yevgeniy Vinogradskiy, Xuanfeng Ding

Department of Radiation Oncology Faculty Papers

Background and purpose: Functional avoidance radiotherapy has emerged as a promising technique using functional imaging to minimize pulmonary toxicity by reducing doses to functional lung. This study aims to investigate the potential dose-volume advantages of a novel spot-scanning proton arc (SPArc) therapy for functional avoidance radiotherapy with four-dimensional computed tomography (4DCT)-based ventilation imaging.

Material and methods: Twenty-five patients from a prospective functional avoidance clinical trial treated with intensity-modulated photon radiotherapy were included. Robustly optimized intensity modulated proton therapy (IMPT) and SPArc plans were generated in RayStation. Functional lung contour was derived from the 4DCT-based ventilation imaging and utilized as an …

Identifying Barriers For Community Pharmacies As Vaccines For Children (Vfc) Providers In Rural Alabama: Opportunities For Solutions, Myra Bajwa

Honors Theses

Significant Human papillomavirus (HPV) vaccination disparities exist between rural and urban areas in the US. A primary contributor is low access to preventive care in rural areas. Among the most promising strategies to overcome this is increasing access through offering HPV vaccination in non-traditional, convenient health settings such as pharmacies. In rural areas, community pharmacies are trusted, convenient pillars of the community. In Alabama, community pharmacies are eligible for enrollment in the Vaccines for Children (VFC) Program, a federally-funded program that provides free vaccines to children and adolescents under 18 years old who are uninsured, underinsured, American Indian, or Alaska …

Enhancing Crna's Knowledge Of Radiation Safety Through Online Education, Angela Iledan, Madeline Pousson

Doctoral Projects

Although ionizing radiation is frequently used in anesthesia-related procedures, many CRNAs receive minimal training in radiation safety principles and protective measures. This knowledge gap increases the risk of cumulative radiation exposure for providers and patients. To address the issue, this doctoral project developed and implemented an online educational intervention designed to enhance CRNAs’ understanding of radiation safety, ultimately promoting safer practices in radiation-prone environments.

The doctoral project follows a QI and EBP approach that incorporated diverse adult learning styles to enhance engagement and knowledge retention of CRNAs. The online educational module was designed and delivered to CRNAs that currently practice …

Exploring Bone Oncology In A Medically Underserved Area: A Retrospective Cohort Of Bone Metastases And Malignant Bone Neoplasia In The Rio Grande Valley, Blake C. Martin, Juan Carlos Lopez Alvarenga, Michael Sander

School of Medicine Publications

Objectives: The Rio Grande Valley (RGV) is a developing clinical research region characterized by its distinctive demographic profile that offers an opportunity to investigate diverse health issues. This pilot investigation sought to evaluate the demographic and clinical characteristics linked to bone metastases and primary malignant bone neoplasms (PMBNs) in patients from the RGV and to compare the frequency of these conditions with the US general population.

Methods: This was a retrospective chart review in which data were gathered from the University of Texas Rio Grande Valley UTHealth electronic database from January 1, 2018 to September 4, 2024. Various statistical analyses …

Blood-Based Clinical Markers For Early Dementia Detection: Insights From Ad-Detect-Cohort, Benard Aliwa, Jasmit Shah, Olivera Nesic Taylor,, Samuel Nguku, Juzar Hooker, Dilraj Sokhi, Sylvia Mbugua, Litha Musili, Rachel Maina, Harrison Kaleli, Levi Muyela, Anne Njoki Gitere, Anne Nyambura, Zul Merali, Karen Blackmon, Chinedu Momoh

Brain and Mind Institute

Background: Over 55 million people worldwide live with dementia, with more than60% residing in low- and middle-income countries. Alzheimer’s disease, the mostcommon form of dementia, accounts for 60–70% of cases. Early and accurate diagnosisremains a global challenge, necessitating novel approaches to mitigate the diseaseburden. Biomarkers hold significant promise in improving diagnostic accuracy andpredicting disease progression. Validated biomarkers for the preclinical stages ofdementia are crucial for advancing diagnosis and therapeutic strategies. We aimedto identify potential clinical markers for early dementia detection and assess theirpredictive accuracy in identifying high-risk individuals.

Method: We analyzed blood samples from dementia cases (n = 30) and …

Cultural Adaptation Of An Innovative Reproductive Health Assessment Tool For Dementia Research In Africa: Insights From The Fember-Africa Study, Alice Moraa Ondieki, Anne Njogu, Cynthia I Sabel Smith, Edna Bosire, Karen Blackmon, Harrison Kaleli, Jasmit Shah, Rachel Maina, Sheila Waa, Chinedu Momoh

Brain and Mind Institute

Background: Dementia research accounts for only 0.1% of all research in Africa,making it the lowest among all low- and middle-income country (LMIC) regions. Thedevelopment and adaptation of biological and psychosocial measures in ethnicallyand culturally diverse populations remain limited but are essential for culturallyinformed research. This is particularly critical for examining sex- and gender-basedvulnerabilities to Alzheimer’s disease and related dementias (ADRD), including factorssuch as reproductive health and fertility.

Method: We conducted a thorough review of our clinical and health questionnaires forcultural relevance and sensitivity through a series (n = 3) of focus groups discussions.These focus groups included a diverse range of …

Bridging The Gut And The Heart-Exploring Pathophysiology, Risk Factors, And Therapeutic Implications Of Cardiovascular Disease In Inflammatory Bowel Disease, Diana Othon-Martinez, Sylvia Valeria Peña-Muñoz, Margarita Riojas-Barrett, Genesis Vidales-López, Josué Moisés Sánchez Guzmán, Lukasz Kwapisz

School of Medicine Publications

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic systemic immune dysregulated disorder affecting the gastrointestinal tract that often has extraintestinal manifestations. Limited data exist on the cardiovascular (CV) implications of IBD, but a higher prevalence of CV disease (CVD) has been observed compared to the general population, resulting in increased mortality risk. This review examines the pathophysiology and risk factors linking IBD to CVD, highlighting several key mechanisms: The “lipid paradox” in active IBD, arterial stiffness and endothelial dysfunction, proinflammatory cytokine activity, gut microbiota dysbiosis, and drug-induced myocardiopathy. The main findings include information about IBD …

Advancing Trypanosoma Cruzi N-Myristoyltransferase As A Drug Target For Chagas Disease Through In Silico Discovery And Biochemical Evaluation, Diana Citlali González García

Open Access Theses & Dissertations

Chagas disease remains one of the most persistent and neglected parasitic infections in the Americas, advancing silently through the intracellular replication of Trypanosoma cruzi amastigotes and the invasive spread of trypomastigotes. The survival of the parasite is critically reliant on protein N-myristoylation, a lipid modification catalyzed by N-myristoyltransferase (NMT). This dissertation aims to advance beyond prior studies by systematically investigating NMT inhibition across multiple biological levels, spanning from the characterization of the purified enzyme, through cellular infection models, to the global proteomic remodeling induced within the parasite, thereby evaluating TcNMT as a potential therapeutic vulnerability in T.cruzi.Recombinant TcNMT was expressed, …

Monte Carlo Simulations Of Geometric Deformation Of Harrison-Anderson-Mick Applicators Used In Intraoperative Radiation Therapy, Benjamin Insley, Brett Bocian, Sam Beddar, Reza Reiazi, Patrick James Jensen, Rachael M Martin-Paulpeter, Joshua Scott Niedzielski, David Flint, Gabriel Oliveira Sawakuchi, Luis Augusto Perles

Faculty, Staff and Student Publications

Background: The Harrison-Anderson-Mick (HAM) applicator is a high-dose-rate intraoperative radiotherapy (HDR-IORT) applicator used to position Ir-192 brachytherapy sources over surgically-accessed tumor volumes or post-resection tumor beds. Because of the lack of a 3D imaging system, dwell times are optimized pre-surgery by a TG-43-based treatment planning system (TPS) that assumes a perfectly flat applicator surface surrounded by an infinite water phantom. These assumed conditions are disparate from typical treatment conditions, especially in the pelvic regions, which often involve uneven patient surfaces and superficial irradiations with little to no backscatter material.

Purpose: Develop and validate a Monte Carlo (MC) model of HDR-IORT …

Adenovirus Types In Us Children Hospitalized Or Seen In The Emergency Department With Acute Respiratory Illness, 2016-2019., Tess Stopczynski, Varvara Probst, Adam Gailani, Justin Z. Amarin, Olla Hamdan, Haya Hayek, Laura S. Stewart, Herdi K. Rahman, Rangaraj Selvarangan, Jennifer E. Schuster, Christopher J. Harrison, Mary E. Moffatt, Marian G. Michaels, John V. Williams, Julie A. Boom, Leila C. Sahni, Vasanthi Avadhanula, Mary Allen Staat, Elizabeth P. Schlaudecker, Christina Quigley, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Aaron T. Curns, Heidi L. Moline, Ariana P. Toepfer, James D. Chappell, Andrew J. Spieker, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Human adenovirus (HAdV) is a common cause of pediatric acute respiratory illness (ARI), contributing to 5-13% of cases worldwide. Clinical manifestations vary by HAdV species and type; therefore, delineating type-specific disease presentations and understanding severity of specific HAdV types' disease may help develop targeted interventions.

METHODS: We conducted a multicenter, prospective study within the New Vaccine Surveillance Network to characterize HAdV types. Children < 18 years old with ARI were enrolled in the emergency department or inpatient setting at 7 US children's hospitals from 1 December 2016 to 30 November 2019. Respiratory specimens were collected and tested for HAdV and other viruses. Subsequently, typing was conducted on HAdV specimens using single-plex real-time PCR assays targeting sequences in the hexon gene. Comparisons between HAdV types were performed to determine differences in characteristics and outcomes. Generalized linear mixed effects models were used to evaluate severity.

RESULTS: Among the 1843 HAdV-positive cases, 1402 specimens (76%) were typed. The most common types detected were HAdV-C1 (n = 439), HAdV-C2 (n = 393), and HAdV-B3 (n = 221). Children with HAdV-B7 (n = 78) …

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Blistering Bulbs: The Hidden Dangers Of Garlic As A Home Remedy., Riley Bunstine, Christopher M Lloyd

Ambulatory and Primary Care Articles

We report a case of a 46-year-old male who developed a second-degree chemical burn after application of crushed raw garlic to his left wrist. When crushed, garlic activates the enzyme alliinase that converts alliin into allicin. In controlled concentrations, allicin has been shown to have a wide array of therapeutic benefits; however, its use as an unregulated home remedy carries a significant risk of toxicity. This patient applied crushed garlic to his left wrist and left this poultice in place for five hours, hoping to ease wrist pain from a previous car accident. Upon removal, he felt an intense burning …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Surgical Removal Of Implanted Microchips To Correct Mri Susceptibility Artifacts In Mice, Elizabeth Hipskind, Nicole Hernandez, Sydney Fox, Tina Manirambona, Rita Schack, Brian Gibson, Robia G Pautler

Center on Aging Staff Publications

Purpose: Implanted microchips are becoming increasingly common in research for animal identification and have been adopted by commercial vendors for some mouse strains. However, they often contain metal components, which generate magnetic susceptibility artifacts on MR images. Despite this, some microchips are marketed as MR-compatible, even though they are likely to affect image quality.

Methods: We assessed the impact of a radiofrequency identification microchip on MR images of the mouse brain and present a method for precise surgical removal. A handheld magnet was used to locate and stabilize the microchips during removal. Mice were imaged before and after microchip removal. …

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

Center on Aging Staff Publications

Objective: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

Methods: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50th percentile Area Deprivation Index, indicating low …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …